Molecular Dynamics Simulation of DNA Stretching Is Consistent with the Tension Observed for Extension and Strand Separation and Predicts a Novel Ladder Structure

Abstract

Molecular dynamics simulations were used to model the response of several double-stranded dodecamers to gradually increasing tension applied to the opposing 3′ ends of the two polynucleotide strands. At forces between 0.80 and 1.45 nN, depending on sequence, the strands separated completely. The separation force for one of the dodecamers studied has been measured and is close to that seen in the simulation. Before strand separation, at forces between 0.065 and 0.090 nN, again depending on sequence, there was an abrupt extension and transition to a novel ladder structure in which bases of one strand were stacked on those of the other strand. Sudden extensions have been observed in very long DNA molecules at forces similar to those seen in the simulations. After the abrupt extension but before strand separation, the ladder structure became more regular, and the phosphate backbones became more linear. Throughout the entire molecular extension, most hydrogen-bonded base pairs remained intact.

Chemical force microscopy of chemical and biological interactions

“…Moreover, the "diluted monolayer" attachment configuration(see Figure 1B) allowed them to detect the mechanical signature corresponding to the structural transition in individual DNA duplexes. This transition to an overstretched S-DNA form (see inset on the Figure 7A for a graphic representation) had been previously observed in macroscopic length DNA in the experiment [47,48], as well as in computer simulations [49,50]. A puzzling feature of the stretching transition observed in the AFM experiment was a relatively high value of 120 pN of the force [20].…”

DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase

“…arginine or ethidium) and a sequence selected from codons yielding phase 1 amino acids was required, with the combination of these two factors operating in a non-additive way to produce a solution structure of stacked base-pair triplets. Overstretching the Σ-duplex led to formation of interdigitated zipper DNA, while stretching without cofactors or appropriate sequence led to disordered but not fully denatured structure consistent with experiments (Balaeff et al 2011;Bosaeus et al 2017) and simulations (Konrad & Bolonick, 1996).…”

“…This is supplemented by fluorescence and polarised-light studies (van Mameren et al 2009;Nordén et al 1992;King et al 2013), and by atomistic simulations which are able to provide explicit descriptions of the DNA but which are limited in the accessible timescales and system sizes (Bag et al 2016;Konrad & Bolonick., 1996;Lebrun & Lavery, 1996;Li & Gisler, 2009;Roe & Chaka, 2009). …”

On structural transitions, thermodynamic equilibrium, and the phase diagram of DNA and RNA duplexes under torque and tension

“…Outstanding examples are the studies of Cluzel et al (17) and Smith et al (18) on stretched DNA (S-DNA), a form 70% longer than B-DNA. The transition was subsequently modeled, with varied abilities to reproduce experimental observables, by computer simulations (19)(20)(21)(22)(23). Additionally, an S-RNA form has also been measured and compared with S-DNA (24).…”